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cd36 overexpression  (Addgene inc)
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Addgene inc cd36 overexpression
Fig. 10 | Schematic of the EC FA export pathway. A The polarized ECs control tissue FA uptake by transcytosis of circulating FAs and their export in small extracellular vesicles (sEVs) to parenchymal cells. FA binding to <t>CD36</t> recruits Src to phosphorylate Cav-1 at tyrosine14, which disrupts the caveolae coat. Associated activation of nSMase2 generates the destabilizing ceramides in the caveolae. Both events initiate caveolae fission from the membrane. The caveolae internalize into small ceramide-rich intracellular vesicles (IVs) thatare then sorted into the lumen of multivesicular bodies (MVBs). The MVBs fuse with the basolateral membrane to release exosome-like small sEVs in the sub-endothelial space. The sEVs export FA and other cargo to parenchymal cells. B Possible alternate fate of endocytosed vesicles in parenchymal cells. The IVs generated in response to FA are likely to be heterogenous and a subset possibly less enriched in specific ceramides might during traffic or sorting associate with proteins such as FABPs that help target the IVs to cellular organelles instead of for secretion as sEVs. This latter fate might predominate in myocytes, cardiomyocytes, and adipocytes where most FAs are kept for local use or storage.
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Fig. 10 | Schematic of the EC FA export pathway. A The polarized ECs control tissue FA uptake by transcytosis of circulating FAs and their export in small extracellular vesicles (sEVs) to parenchymal cells. FA binding to CD36 recruits Src to phosphorylate Cav-1 at tyrosine14, which disrupts the caveolae coat. Associated activation of nSMase2 generates the destabilizing ceramides in the caveolae. Both events initiate caveolae fission from the membrane. The caveolae internalize into small ceramide-rich intracellular vesicles (IVs) thatare then sorted into the lumen of multivesicular bodies (MVBs). The MVBs fuse with the basolateral membrane to release exosome-like small sEVs in the sub-endothelial space. The sEVs export FA and other cargo to parenchymal cells. B Possible alternate fate of endocytosed vesicles in parenchymal cells. The IVs generated in response to FA are likely to be heterogenous and a subset possibly less enriched in specific ceramides might during traffic or sorting associate with proteins such as FABPs that help target the IVs to cellular organelles instead of for secretion as sEVs. This latter fate might predominate in myocytes, cardiomyocytes, and adipocytes where most FAs are kept for local use or storage.

Journal: Nature communications

Article Title: Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels.

doi: 10.1038/s41467-023-39752-3

Figure Lengend Snippet: Fig. 10 | Schematic of the EC FA export pathway. A The polarized ECs control tissue FA uptake by transcytosis of circulating FAs and their export in small extracellular vesicles (sEVs) to parenchymal cells. FA binding to CD36 recruits Src to phosphorylate Cav-1 at tyrosine14, which disrupts the caveolae coat. Associated activation of nSMase2 generates the destabilizing ceramides in the caveolae. Both events initiate caveolae fission from the membrane. The caveolae internalize into small ceramide-rich intracellular vesicles (IVs) thatare then sorted into the lumen of multivesicular bodies (MVBs). The MVBs fuse with the basolateral membrane to release exosome-like small sEVs in the sub-endothelial space. The sEVs export FA and other cargo to parenchymal cells. B Possible alternate fate of endocytosed vesicles in parenchymal cells. The IVs generated in response to FA are likely to be heterogenous and a subset possibly less enriched in specific ceramides might during traffic or sorting associate with proteins such as FABPs that help target the IVs to cellular organelles instead of for secretion as sEVs. This latter fate might predominate in myocytes, cardiomyocytes, and adipocytes where most FAs are kept for local use or storage.

Article Snippet: For CD36 overexpression, mEmerald-CD36 (Addgene, #54030) and mCherry-Cav-1 (Addgene, #55008) were transfected with Lipofectamaine LTX (ThermoFisher Scientific).

Techniques: Control, Binding Assay, Activation Assay, Membrane, Generated